3-Carene, a Phytoncide from Pine Tree Has a Sleep-enhancing Effect by Targeting the GABA(A)-benzodiazepine Receptors
- Author:
Junsung WOO
1
;
Hyejin YANG
;
Minseok YOON
;
Changdev G GADHE
;
Ae Nim PAE
;
Suengmok CHO
;
C Justin LEE
Author Information
- Publication Type:Original Article
- Keywords: 3-carene; Sleep; GABA(A)-BZD receptor; Phytoncide
- MeSH: Administration, Oral; Anti-Anxiety Agents; Flumazenil; Hypnotics and Sedatives; Oils, Volatile; Pinus
- From:Experimental Neurobiology 2019;28(5):593-601
- CountryRepublic of Korea
- Language:English
- Abstract: 3-Carene, a bicyclic monoterpene, is one of the major components of the pine tree essential oils. It has been reported that, in addition to its known properties as a phytoncide, 3-carene has anti-inflammatory, antimicrobial, and anxiolytic effects. We have previously demonstrated that α-pinene, the major component of pine tree, has a hypnotic effect through GABA(A)-benzodiazepine (BZD) receptors. However, a hypnotic effect of 3-carene has not been studied yet. Here, we report that oral administration of 3-carene increases the sleep duration and reduces sleep latency in pentobarbital-induced sleep test. 3-Carene potentiates the GABA(A) receptor-mediated synaptic responses by prolonging the decay time constant of inhibitory synaptic responses. These enhancing effects of 3-carene are reproduced by zolpidem, a modulator for GABA(A)-BZD receptor, and fully inhibited by flumazenil, an antagonist for GABA(A)-BZD receptor. The molecular docking of 3-carene to the BZD site of GABA(A) protein structure, suggests that 3-carene binds to the BZD site of α1 and ϒ2 subunits of GABA(A)-BZD receptor. These results indicate that, similar to α-pinene, 3-carene shows a sleep-enhancing effect by acting as a positive modulator for GABA(A)-BZD receptor.
